Starting from the antimalarial drugs chloroquine and hydroxychloroquine, we conducted a structural optimization on the side chain of chloroquine by introducing amino substituted longer chains thus leading to a series of novel aminochloroquine derivatives. Anti-infectious effects against SARS-Cov2 spike glycoprotein as well as immunosuppressive and anti-inflammatory activities of the new compounds were evaluated. Distinguished immunosuppressive activities on the responses of T cell, B cell and macrophages upon mitogen and pathogenic signaling were manifested. Compounds 9–11 displayed the most promising inhibitory effects both on cellular proliferation and on the production of multiple pro-inflammatory cytokines, including IL-17, IFN-γ, IL-6, IL-1β and TNF-α, which might be insightful in the pursuit of treatment for immune disorders and inflammatory diseases.

我们以抗疟药氯喹和羟氯喹为出发点，通过引入氨基取代长链，对氯喹的侧链进行结构优化，得到一系列新型氨基氯喹衍生物。评估了新化合物对 SARS-Cov2 刺突糖蛋白的抗感染作用以及免疫抑制和抗炎活性。对 T 细胞、B 细胞和巨噬细胞对有丝分裂原和致病信号的反应表现出独特的免疫抑制活性。化合物9 – 11对细胞增殖和多种促炎细胞因子（包括 IL-17、IFN-γ、IL-6、IL-1β 和 TNF-α）的产生均显示出最有希望的抑制作用，这可能对追求治疗免疫紊乱和炎症性疾病。